Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection.

Journal Article

Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18-45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 10(4) versus 5 × 10(4) PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 μL versus 50 μL) were studied. Three groups attained 100% infection: 1 × 10(4) PfSPZ in 50 μL/2 doses, 1 × 10(4) PfSPZ in 10 μL/2 doses, and 5 × 10(4) PfSPZ in 10 μL/8 doses. The group that received 5 × 10(4) PfSPZ total dose in eight 10 μL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes.

Full Text

Duke Authors

Cited Authors

  • Lyke, KE; Laurens, MB; Strauss, K; Adams, M; Billingsley, PF; James, E; Manoj, A; Chakravarty, S; Plowe, CV; Li, ML; Ruben, A; Edelman, R; Green, M; Dube, TJ; Sim, BKL; Hoffman, SL

Published Date

  • December 2015

Published In

Volume / Issue

  • 93 / 6

Start / End Page

  • 1274 - 1284

PubMed ID

  • 26416102

Electronic International Standard Serial Number (EISSN)

  • 1476-1645

International Standard Serial Number (ISSN)

  • 0002-9637

Digital Object Identifier (DOI)

  • 10.4269/ajtmh.15-0341

Language

  • eng